Hirota, Yuki

写真a

Affiliation

School of Medicine, Department of Anatomy （Shinanomachi）

Position

Assistant Professor/Senior Assistant Professor

External Links
Page Top ▲
 

Research Areas 【 Display / hide 】

  • Life Science / Developmental biology

Page Top ▲

Research Keywords 【 Display / hide 】

  • 大脳皮質発生

  • 神経細胞移動

Page Top ▲

Research Themes 【 Display / hide 】

  • developmental biology of brain, 

    2007.01
    -
    Present

Page Top ▲
 

Books 【 Display / hide 】

  • Tumors of the Central Nervous System. Volume 9.

    Hirota Yuki, Springer, 2012.01

    Scope: Proliferation of Neuroblasts in the Adult Brain: Role of Diversin

  • Neurogenesis in the adult brain I: Neurobiology.

    Hirota Yuki, Springer, 2011.01

    Scope: Neuronal migration in the adult brain.

  • Neural Development.

    Hirota Yuki, Springer-Verlag, 1999.01

    Scope: The regulatory mechanisms of neural development: roles of cell-aoutonomous and non-cell-autonomous cues in cell-fate decisions.

Page Top ▲

Papers 【 Display / hide 】

  • The secreted glycoprotein reelin suppresses the proliferation and regulates the distribution of oligodendrocyte progenitor cells in the embryonic neocortex

    Ogino H., Nakajima T., Hirota Y., Toriuchi K., Aoyama M., Nakajima K., Hattori M.

    Journal of Neuroscience （Journal of Neuroscience)  40 （ 40 ） 7625 - 7636 2020.09

    ISSN  02706474

    　View Summary

    Copyright © 2020 the authors. Oligodendrocyte (OL) progenitor cells (OPCs) are generated, proliferate, migrate, and differentiate in the developing brain. Although the development of OPCs is prerequisite for normal brain function, the molecular mechanisms regulating their development in the neocortex are not fully understood. Several molecules regulate the tangential distribution of OPCs in the developing neocortex, but the cue molecule(s) that regulate their radial distribution remains unknown. Here, we demonstrate that the secreted glycoprotein Reelin suppresses the proliferation of OPCs and acts as a repellent for their migration in vitro. These functions rely on the binding of Reelin to its receptors and on the signal transduction involving the intracellular protein Dab1. In the late embryonic neocortex of mice with attenuated Reelin signaling [i.e., Reelin heterozygote-deficient, Dab1 heterozygote-deficient mutant, or very low-density lipoprotein receptor (VLDLR)-deficient mice], the number of OPCs increased and their distribution shifted toward the superficial layers. In contrast, the number of OPCs decreased and they tended to distribute in the deep layers in the neocortex of mice with abrogated inactivation of Reelin by proteolytic cleavage, namely a disintegrin and metalloproteinase with thrombospondin type 1 motifs 3 (ADAMTS-3)-deficient mice and cleavage-resistant Reelin knock-in mice. Both male and female animals were used. These data indicate that Reelin–Dab1 signaling regulates the proliferation and radial distribution of OPCs in the late embryonic neocortex and that the regulation of Reelin function by its specific proteolysis is required for the normal development of OPCs.

  • VLDLR is not essential for reelin-induced neuronal aggregation but suppresses neuronal invasion into the marginal zone.

    Hirota Y, Nakajima K.

    Development （Development (Cambridge))  in press （ 12 ）  2020

    Research paper (scientific journal), Joint Work, Accepted,  ISSN  09501991

    　View Summary

    © 2020. Published by The Company of Biologists Ltd In the developing neocortex, radially migrating neurons stop migration and form layers beneath the marginal zone (MZ). Reelin plays essential roles in these processes via its receptors, apolipoprotein E receptor 2 (ApoER2) and very low density lipoprotein receptor (VLDLR). Although we recently reported that reelin causes neuronal aggregation via ApoER2, which is thought to be important for the subsequent layer formation, it remains unknown what effect reelin exerts via the VLDLR. Here, we found that ectopic reelin overexpression in the Vldlr-mutant mouse cortex causes neuronal aggregation, but without an MZ-like cell-sparse central region that is formed when reelin is overexpressed in the normal cortex. We also found that both the early-born and late-born Vldlr-deficient neurons invade the MZ and exhibit impaired dendrite outgrowth from before birth. Rescue experiments indicate that VLDLR suppresses neuronal invasion into the MZ via a cell-autonomous mechanism, possibly mediated by Rap1, integrin and Akt. These results suggest that VLDLR is not a prerequisite for reelin-induced neuronal aggregation and that the major role of VLDLR is to suppress neuronal invasion into the MZ during neocortical development.

  • ApoER2 Controls Not Only Neuronal Migration in the Intermediate Zone But Also Termination of Migration in the Developing Cerebral Cortex

    Hirota Yuki

    Cereb Cortex （Cerebral Cortex)  28 （ 1 ） 223 - 235 2018.01

    Research paper (scientific journal), Joint Work, Accepted,  ISSN  1460-2199

    　View Summary

    © The Author 2016. Published by Oxford University Press. All rights reserved. Neuronal migration contributes to the establishment of mammalian brain. The extracellular protein Reelin sends signals to various downstream molecules by binding to its receptors, the apolipoprotein E receptor 2 (ApoER2) and very low-density lipoprotein receptor and exerts essential roles in the neuronal migration and formation of the layered neocortex. However, the cellular and molecular functions of Reelin signaling in the cortical development are not yet fully understood. Here, to gain insight into the role of Reelin signaling during cortical development, we examined the migratory behavior of Apoer2-deficient neurons in the developing brain. Stage-specific labeling of newborn neurons revealed that the neurons ectopically invaded the marginal zone (MZ) and that neuronal migration of both early- and late-born neurons was disrupted in the intermediate zone (IZ) in the Apoer2 KO mice. Rescue experiments showed that ApoER2 functions both in cell-autonomous and noncell-autonomous manners, that Rap1, integrin, and Akt are involved in the termination of migration beneath the MZ, and that Akt also controls neuronal migration in the IZ downstream of ApoER2. These data indicate that ApoER2 controls multiple processes in neuronal migration, including the early stage of radial migration and termination of migration beneath the MZ in the developing neocortex.

  • Control of Neuronal Migration and Aggregation by Reelin Signaling in the Developing Cerebral Cortex

    Hirota Yuki

    Frontiers in Cell and Developmental Biology 5 （ 40 ）  2017.04

    Research paper (scientific journal), Joint Work, Accepted,  ISSN  2296-634X

  • Roles of Wnt Signaling in the Neurogenic Niche of the Adult Mouse Ventricular-Subventricular Zone

    Hirota, Yuki, Sawada, Masato, Huang, Shih-hui, Ogino, Takashi, Ohata, Shinya, Kubo, Akiharu, Sawamoto, Kazunobu

    NEUROCHEMICAL RESEARCH 41 （ 1-2 ） 222 - 230 2016.02

    Research paper (scientific journal),  ISSN  0364-3190

display all >>

Page Top ▲

Papers, etc., Registered in KOARA 【 Display / hide 】

display all >>

Page Top ▲

Presentations 【 Display / hide 】

  • リーリンシグナルによるニューロン移動停止制御機構

    廣田ゆき, 仲嶋一範.

    第124回日本解剖学会総会全国学術集会, 

    2019.03
    , 

    Oral presentation (general)

  • リーリンシグナルによるニューロン移動停止制御機構

    廣田ゆき, 仲嶋一範.

    第41回日本分子生物学会年会 (横浜) , 

    2018.11
    , 

    Symposium, workshop panel (nominated)

  • 大脳皮質発生におけるリーリンシグナルの機能

    廣田ゆき, 仲嶋一範.

    2018年度生理学研究所研究会「神経発達・再生研究会」, 

    2018.10
    , 

    Oral presentation (invited, special)

  • How does Reelin signaling control the termination of neuronal migration?

    Yuki Hirota, Kazunori Nakajima

    第40回日本生物学的精神医学会・第61回日本神経化学会大会 (神戸) , 

    2018.09
    , 

    Oral presentation (general)

  • ApoER2 controls not only neuronal migration but also termination of migration in the developing cerebral cortex”

    Hirota Yuki

    22nd Biennial Meeting of the International Society for Developmental Neuroscience (Nara) , 

    2018.05
    , 

    Poster presentation

display all >>

Page Top ▲

Research Projects of Competitive Funds, etc. 【 Display / hide 】

  • 大脳皮質形成において神経細胞が移動を停止し配置する機構の解明

    2023.04
    -
    2027.03

    基盤研究(B), Principal investigator

  • ニューロン反発因子を介した大脳皮質形成機構

    2020.04
    -
    2023.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), Principal investigator

  • 大脳皮質層構造形成を司る糖蛋白質リーリンの受容体VLDLRを介した発生および病態時におけるニューロン移動制御機構

    2018
    -
    2019

    鈴木謙三記念医科学応用研究財団, 平成30年度調査研究助成, Other, Principal investigator

  • 受容体複合体による皮質ニューロン移動制御機構

    2017.04
    -
    2020.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), Principal investigator

  • 大脳皮質形成における樹状突起伸長を介した移動ニューロン配置決定機構

    2017
    -
    Present

    武田科学振興財団, 2017年度 医学系研究奨励, Principal investigator

display all >>

Page Top ▲

Awards 【 Display / hide 】

  • 公益信託成茂神経科学研究助成基金平成25年度研究助成

    2013.05, 公益信託成茂神経科学研究助成基金, マウス大脳皮質形成過程におけるリーリンシグナルの移動ニューロンへの作用機序

    Type of Award： Award from publisher, newspaper, foundation, etc.

  • 平成22年度名古屋市立大学医学会賞

    2010.12, 名古屋市立大学医学会, 非筋細胞ミオシンⅡによるマウス上衣細胞絨毛の平面極性制御

    Type of Award： Award from Japanese society, conference, symposium, etc.

Page Top ▲
 

Courses Taught 【 Display / hide 】

  • HUMAN ANATOMY AND PHYSIOLOGY

    2024

  • EMBRYOLOGY

    2024

  • ANATOMY AND EMBRYOLOGY 2

    2024

  • ANATOMY

    2024

  • EMBRYOLOGY

    2023

display all >>

Page Top ▲

Courses Previously Taught 【 Display / hide 】

  • 発生学

    Keio University

    2018.04
    -
    2019.03
    , 

    Within own ｆaculty

  • 神経解剖学

    Keio University

    2018.04
    -
    2019.03
    , 

    Within own ｆaculty

  • 肉眼解剖学

    Keio University

    2018.04
    -
    2019.03
    , 

    Lecture

  • 発生学

    慶應義塾大学医学部

    2018.04
    -
    2019.03

  • 神経解剖学

    慶應義塾大学医学部

    2018.04
    -
    2019.03

display all >>

Page Top ▲
 

Social Activities 【 Display / hide 】

  • 慶應義塾大学第40回四谷祭 研究室ツアー

    2017.11
    -
    Present

  • 慶應義塾大学医学部解剖学教室仲嶋研究室オープンラボ

    2017.08
    -
    Present

  • 日本学術振興会ひらめきときめきサイエンスプログラム「脳の中で生まれる神経細胞〜脳のできるしくみと医療への応用〜」（名古屋市立大学医学研究科再生医学分野）

    2010.08
    -
    Present

  • 慶應義塾大学医学部ブリヂストン神経発生・再生学寄附講座 市民公開講座「交通外傷と神経再生」.

    2006.03
    -
    Present
Page Top ▲

Memberships in Academic Societies 【 Display / hide 】

  • 日本分子生物学会

    　

  • 日本神経化学会

    　

  • 日本神経科学会

    　

  • 日本解剖学会

    　
Page Top ▲

Committee Experiences 【 Display / hide 】

  • 2017.07
    -
    Present

    出版・広報委員会, 日本神経化学会

Page Top ▲